Phototransduction in vertebrate rods and cones consists of a series of precisely timed events that are necessary for photoreceptors to function under a broad range of light intensities. While rods operate under dim light and are easily saturated in response to bright light, cones recover more rapidly and are able to adapt to much more intense light. Second messengers, such as cGMP and Ca2+, are already well-known to play important roles in the phototransduction cascade and adaptation in rods and cones. Another second messenger, cAMP, which is regulated both in a light- and a circadian-dependent manner in photoreceptors, may also be important for adaptation. For example, changes in cAMP synthesis are associated with defects in adaptation in rods and cones that alter signaling to the inner retina. Interestingly, phosphorylation of photoreceptor cell proteins by PKA, the downstream target of cAMP, has not been well-studied. We have determined that the retina-specific G protein-coupled receptor kinases, GRK1 and GRK7, which play critical roles in recovery and adaptation in rods and cones, are both substrates for PKA in vitro. We have also shown that phosphorylation by PKA reduces the ability of these kinases to phosphorylate their substrates, the opsins in vitro. In this proposal, we provide new evidence that both kinases are phosphorylated by PKA in vivo and that phosphorylation is regulated by light. We propose to use the mouse as a model to study the functional consequences of GRK1 phosphorylation by PKA on its role in recovery and adaptation. Our data introduce a novel mechanism for the regulation of photoreceptor cell- specific GRKs that may influence multiple facets of phototransduction.